Association between remnant cholesterol and the risk of cardiovascular-kidney-metabolic syndrome progression: insights from the China health and retirement longitudinal study

AIMS: Advanced cardiovascular-kidney-metabolic (CKM) syndrome has profound impacts on adverse clinical outcomes, particularly cardiovascular disease (CVD). Remnant cholesterol (RC) has emerged as a potential risk factor for metabolic and cardiovascular disorders, but its association with CKM syndrome remains unexplored. This study aimed to investigate the relationship between RC and CKM syndrome progression. METHODS AND RESULTS: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011-20. Logistic regression models were conducted to estimate the association between RC and advanced CKM stages at baseline. Cox regression models were employed to assess the association between baseline RC and incident CVD during follow-up. In the baseline analysis, individuals in higher RC quartiles (Q2-Q4) had a significantly increased risk of advanced CKM stages compared to the lowest RC quartile (Q1) (P for trend <0.001). During the median follow-up period of 9.0 years, 1498 participants (21.8%) across CKM Stages 0-3 developed CVD. After multivariable adjustment, per 1-SD increase in RC was associated with a higher risk of CVD. Similarly, in quartile analyses, the risk of CVD remained elevated in the Q3 [hazard ratio (HR) 1.181, 95% confidence interval (CI) 1.021-1.366] and Q4 (HR 1.195, 95% CI 1.032-1.383) groups compared to the first RC quartile group. CONCLUSION: Elevated RC was independently associated with advanced CKM stages. Furthermore, among individuals with CKM syndrome without baseline CVD, elevated RC emerged as a significant risk factor for incident CVD. Early detection and management of RC may provide clinical benefits for preventing CKM progression.